title: Synthesis of pharmacologically active 1-amino-isoquinolines prepared via silver triflate-catalyzed cyclization of o-alkynylbenzaldoximes with isocyanates.
abstract: The synthesis of a series of 1-amino-isoquinolines prepared via electrophilic cyclization [3+2] cycloaddition/rearrangement reactions of o-alkynylbenzaldoxime 1 with isocyanates 2 in the presence of catalytic amount of AgOTf was demonstrated. The cyclized products were obtained in good yields under an air atmosphere. 1-Amino-isoquinoline derivatives 3a, 3b, 3j and 3t were screened in vitro for the antioxidant potential and efficacy to inhibit cerebral monoamine oxidase (MAO) activity. The antidepressant-like action of some 1-amino-isoquinolines was performed in the mouse forced swimming test (FST). The pharmacological screening of 1-amino-isoquinoline derivatives indicated that 3a, 3b, 3j and 3t were antioxidants and inhibited cerebral MAO-A and B activities at low concentrations. Although at different doses 3a, 3b, 3j and 3t were effective antidepressant-like drugs in the mouse FST. None of 1-amino-isoquinolines tested caused acute cerebral, hepatic or renal toxicity in mice.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, RS, Brazil.
authors.forename: Anderson C
authors.initials: AC
authors.lastname: Mantovani
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Pesarico
authors.forename: Tuane B
authors.initials: TB
authors.lastname: Sampaio
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D002384:Catalysis; D003500:Cyclization; D017953:Isocyanates / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D008698:Mesylates / Q000737:chemistry*; D051379:Mice; D008995:Monoamine Oxidase / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D000928:Antidepressive Agents; D017953:Isocyanates; D007546:Isoquinolines; D008698:Mesylates; D008995:Monoamine Oxidase; C012077:trifluoromethanesulfonic acid; C041545:1-aminoisoquinoline
keywords: Antidepressant-like; Antioxidant; Cyclization reaction; Isoquinolines; Silver cycloaddition